Human skin is composed of three primary layers, the stratum corneum, the epidermis, and the dermis. The outer layer is the stratum corneum. Its primary function is to serve as a barrier to the external environment. Lipids are secreted to the surface of the stratum corneum. These lipids decrease the stratum corneum's water permeability. Sebum typically constitutes 95% of these lipids. Abramovits et al, Dermatologic Clinics, Vol 18, Number 4, October 2000.
Sebum is produced in the sebaceous glands. These glands are present over most of the surface of the body. The highest concentration of these glands occurs on the scalp, the forehead and the face. Despite the important physiological role that sebum plays, many individuals experience excess sebum production, especially in the facial area. Excess sebum is associated with an increased incidence of acne. Even in individuals without acne, sebum can make the skin look greasy, decreasing its attractiveness. Abramovits et al, supra.
Acyl CoA cholesterol acyl transferase (ACAT) inhibitors were initially evaluated to treat elevated cholesterol. U.S. Pat. No. 6,133,326 discloses that in addition to lowering cholesterol, ACAT inhibitors reduce the secretion of sebum. Co-pending, commonly assigned, U.S. patent application Ser. No. 10/958,306 having an effective filing date of Oct. 9, 2003, discloses the use of a specific class of diamide ACAT inhibitors in the reduction of sebum. N-benzyl-N′-(2,6-diisopropyl-phenyl)-N-isopropyl-malonamide is one of the compounds whose use is exemplified in the '306 application. N-benzyl-N′-(2,6-diisopropyl-phenyl)-N-isopropyl-malonamide was initially described in European patent application 0 433 662 (see page 11, line 50, where it is referred to as N′-[2,6-bis(1-methylethyl)-phenyl]-N-(1-methylethyl)-N -(phenylmethyl)propanediamide) as an ACAT inhibitor for the treatment of elevated cholesterol. The European '662 application does not disclose the use of these compounds to control sebum secretion.